US2010062465A1PendingUtilityA1

Detection of Histone Deacetylase Inhibition

Individually held — no corporate assignee on recordPriority: Apr 21, 2006Filed: Apr 20, 2007Published: Mar 11, 2010
Est. expiryApr 21, 2026(expired)· nominal 20-yr term from priority
A61K 49/10A61K 31/325
52
PatentIndex Score
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Cited by
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Claims

Abstract

Provided are compositions and methods for intracellular detection of enzyme activity. One example of a composition is a histone deacetylase substrate comprising a compound of the following formula (I): One example of a method is a method for detecting histone deacetylase activity comprising introducing a compound according to formula (1) to a plurality of cells and monitoring the cells with magnetic resonance spectroscopy.

Claims

exact text as granted — not AI-modified
1 . A histone deacetylase substrate comprising a compound of the following formula (I): 
     
       
         
         
             
             
         
       
     
   
   
       2 . A composition formed from the activity of histone deacetylase on the deacetylase substrate of  claim 1 . 
   
   
       3 . A histone deacetylase inhibitor comprising a compound represented by formula (II): 
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , and R 3  individually represent an F or H, and R 4  represents NHOH or OEt. 
     
   
   
       4 . The histone deacetylase inhibitor of  claim 3  wherein R 1  represents F, R 2  represents H, R 3  represents H, and R 4  represents NHOH. 
   
   
       5 . The histone deacetylase inhibitor of  claim 3  wherein R 1  represents H, R 2  represents F, R 3  represents H, and R 4  represents NHOH. 
   
   
       6 . The histone deacetylase inhibitor of  claim 3  wherein R 1  represents H, R 2  represents H, R 3  represents F, and R 4  represents NHOH. 
   
   
       7 . The histone deacetylase inhibitor of  claim 3  wherein R 1  represents F, R 2  represents H, R 3  represents H, and R 4  represents OEt. 
   
   
       8 . The histone deacetylase inhibitor of  claim 3  wherein R 1  represents H, R 2  represents F, R 3  represents H, and R 4  represents OEt. 
   
   
       9 . The histone deacetylase inhibitor of  claim 3  wherein R 1  represents H, R 2  represents H, R 3  represents F, and R 4  represents OEt. 
   
   
       10 . A histone deacetylase inhibitor comprising a compound represented by formula (III): 
     
       
         
         
             
             
         
       
     
   
   
       11 . A histone deacetylase inhibitor comprising a compound represented by formula (IV): 
     
       
         
         
             
             
         
       
     
   
   
       12 . A method for detecting histone deacetylase activity comprising introducing a compound according to  claim 1  to a plurality of cells and monitoring the cells with magnetic resonance spectroscopy. 
   
   
       13 . The method of  claim 12  wherein the cells are monitored for cleavage of the compound according to  claim 1 . 
   
   
       14 . The method of  claim 12  further comprising introducing a histone deacetylase inhibitor to the cells. 
   
   
       15 . The method of  claim 12  wherein the cells are monitored for a change in a biomarker chosen from at least one of a cellular metabolite, phosphocholine, and glycerophosphocholine. 
   
   
       16 . The method of  claim 12  wherein the magnetic resonacne spectroscopy is chosen from at least one of  19 F magnetic resonacne spectroscopy,  31 P magnetic resonacne spectroscopy, and  1 H magnetic resonacne spectroscopy. 
   
   
       17 . The method of  claim 12  further comprising introducing a therapeutic agent or a histone deacetylase inhibitor or both to the cells before monitoring the cells with magnetic resonance spectroscopy. 
   
   
       18 . The method of  claim 17  wherein the therapeutic agent is a histone deacetylase inhibitor.

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